Direct, noninvasive measurement of brain glycogen metabolism in humans

Öz, Gülin; Henry, Pierre Gilles; Seaquist, Elizabeth R.; Gruetter, Rolf

doi:10.1016/s0197-0186(03)00019-6

Cited by 80 publications

(30 citation statements)

References 46 publications

(58 reference statements)

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“…Thus, glycogenolysis rate in awake, unstimulated rodents is about 1% of the rate of utilization of blood-borne glucose in cerebral cortex (Sokoloff et al 1977). Calculated rates of glycogen turnover determined in magnetic resonance studies with [ 13 C]glucose in resting human (~0.003 mol/g/min (Öz et al 2003)) and rat (~0.007-0.01 mol/g/min (van Heeswijk et al 2010; Choi et al 1999) brain are also extremely low. When these data are considered within the context of negligible effects of inhibition of glycogen phosphorylase on compensatory changes in CMR glc in resting animals (Dienel et al 2007a), it is reasonable to conclude that basal turnover of glycogen has barely detectable contributions to overall brain energetics in non-stimulated subjects.…”

Section: Rates Of Glycogenolysismentioning

confidence: 98%

Contributions of glycogen to astrocytic energetics during brain activation

Dienel

Cruz

2014

Metab Brain Dis

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Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

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Section: Rates Of Glycogenolysismentioning

confidence: 98%

Contributions of glycogen to astrocytic energetics during brain activation

Dienel

Cruz

2014

Metab Brain Dis

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“…In spite of this theoretical 150 g surplus of carbohydrate, only an extra 17 g of glycogen was stored (net) in the liver, and no additional glycogen was stored (net) in muscle (numerical difference of <0.9 g·kg muscle −1 ). It could be speculated that the additional carbohydrate was either oxidised, converted to lipid and/or stored in minor amounts in other glycogen containing tissues such as the kidneys, brain, heart and even adipose tissue [97,98,99]. Fructose plus glucose ingestion accelerates liver glycogen repletion rates over glucose ingestion alone.…”

Section: Glucose–fructose Co-ingestion and Recovery From Exercisementioning

confidence: 99%

Glucose Plus Fructose Ingestion for Post-Exercise Recovery—Greater than the Sum of Its Parts?

et al. 2017

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Carbohydrate availability in the form of muscle and liver glycogen is an important determinant of performance during prolonged bouts of moderate- to high-intensity exercise. Therefore, when effective endurance performance is an objective on multiple occasions within a 24-h period, the restoration of endogenous glycogen stores is the principal factor determining recovery. This review considers the role of glucose–fructose co-ingestion on liver and muscle glycogen repletion following prolonged exercise. Glucose and fructose are primarily absorbed by different intestinal transport proteins; by combining the ingestion of glucose with fructose, both transport pathways are utilised, which increases the total capacity for carbohydrate absorption. Moreover, the addition of glucose to fructose ingestion facilitates intestinal fructose absorption via a currently unidentified mechanism. The co-ingestion of glucose and fructose therefore provides faster rates of carbohydrate absorption than the sum of glucose and fructose absorption rates alone. Similar metabolic effects can be achieved via the ingestion of sucrose (a disaccharide of glucose and fructose) because intestinal absorption is unlikely to be limited by sucrose hydrolysis. Carbohydrate ingestion at a rate of ≥1.2 g carbohydrate per kg body mass per hour appears to maximise post-exercise muscle glycogen repletion rates. Providing these carbohydrates in the form of glucose–fructose (sucrose) mixtures does not further enhance muscle glycogen repletion rates over glucose (polymer) ingestion alone. In contrast, liver glycogen repletion rates are approximately doubled with ingestion of glucose–fructose (sucrose) mixtures over isocaloric ingestion of glucose (polymers) alone. Furthermore, glucose plus fructose (sucrose) ingestion alleviates gastrointestinal distress when the ingestion rate approaches or exceeds the capacity for intestinal glucose absorption (~1.2 g/min). Accordingly, when rapid recovery of endogenous glycogen stores is a priority, ingesting glucose–fructose mixtures (or sucrose) at a rate of ≥1.2 g·kg body mass−1·h−1 can enhance glycogen repletion rates whilst also minimising gastrointestinal distress.

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“…Targeting research on brain glycogen pathways will be promising for both diagnosis and therapy. However, in terms of diagnosis, the in vivo measurement of brain glycogen content and synthesis is a challenge for the future, although the use of injection of [1- 13 ]C-glucose has made possible the non-invasive measurement of brain glycogen content and turnover in both humans [145, 146] and rats [132, 133, 147-149]. These advances in the determination of brain glycogen will create a new understanding of its functions, roles and metabolism in both normal and in pathological conditions [110, 111, 130, 131, 150].…”

Section: Neural Cells Neurotransmission Energy Metabolismmentioning

confidence: 99%

Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission

Cloix

Hevor

2009

CMC

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Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most “resistant” strain to methionine sulfoximine, while CBA/J is the most “sensitive” one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.

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Direct, noninvasive measurement of brain glycogen metabolism in humans

Cited by 80 publications

References 46 publications

Contributions of glycogen to astrocytic energetics during brain activation

Contributions of glycogen to astrocytic energetics during brain activation

Glucose Plus Fructose Ingestion for Post-Exercise Recovery—Greater than the Sum of Its Parts?

Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission

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